The major hypothesis guiding this study is that near-infrared (NIR) fluorescence imaging has the potential to improve human cancer surgery by providing sensitive, specific, and real-time intraoperative visualization of normal and disease processes. The Pi's laboratory has developed a low-cost, safe, and easy to use NIR fluorescence imaging system that permits the surgeon to see surgical anatomy and invisible NIR fluorescence simultaneously, in real-time, and with high spatial resolution. To translate this technology to the clinic, we have established a Bioengineering Research Partnership (BRP) comprised of members of the Pi's laboratory, academic veterinary surgeons at the Purdue University School of Veterinary Medicine, and our industrial partner GE Healthcare. GE is committed to translating the imaging system to the clinic, and will provide their extensive expertise in biomedical system design and implementation. GE and the BIDMC have also signed a model agreement concerning intellectual property and shared development, which ensures that academic and industrial resources are fully leveraged during technology translation. The end-point of our study will be the development of an intraoperative NIR fluorescence imaging system ready for human clinical trials. To achieve this goal, we describe a systematic series of small and large animal studies, and a closed-loop feedback development process designed to optimize each system component. The timeline for our study is as follows: Project Year (PY) 1 - initial design of the prototype imaging system for open surgeries. PY 2 - addition of endoscopy/laparoscopy capabilities for minimally invasive surgery. PY 3 - addition of optical diffusion technology to the open surgery system. PY 4 - final prototype development for the open and minimally-invasive imaging systems, and PY Ji - final optimization of system components and software, final validation studies, and preparation for translation to the clinic. Immediate cancer surgery applications of the imaging system include image-guided sentinel lymph node mapping, image-guided cancer resection with real-time assessment of surgical margins, and intraoperative detection of occult metastases in the surgical field. The imaging system will also ensure that critical structures such as nerves and blood vessels are visualized and avoided. Taken together, this BRP application describes an academic/industrial partnership engineered for successful translation of a general-purpose optical imaging technology to the clinic.